Method of producing alpha-acetyl propionitrile



United States Patent O METHOD OF PRODUCING u-ACETYL PROPIONITRILE Hideo' Okeda, Kanji Taniguchi, Aritsune Kaji, and Kazuo Abe, Takaoka City, Japan, assignors to Nippon Soda Co. Ltd., Tokyo, Japan Application September 4, 1957 Serial No. 681,883

11 Claims. (Cl. 260-4651) No Drawing.

desired compound. (Journal fiir Praktische Chemie, (2)

By another reported method, 3-chIorobutanone-(2), which was obtained by the chlorination'of methylethylketone, is-allowed to react'with an alkali metal cyanide, suchas sodium cyanide or potassium, cyanide. This reaction may be carried out in absolute alcohol (Bulletin de la Socit Chimique de France, (3) 6, 814 (1891)), or in aqueous medium (Chemisches Zentralblatt, 1900, l, 1123; 1901','1,'95),.'

2,830,07i Patented Apr. 8 195$ following detailed description and from the various illustrative examples included herein.

In accordance with the present invention, low priced methylethylketone was used as one of the starting mate- 6 rials. It was found that ot-acetylpropionitrile could be ob- Thefirst method has little commercial value'because of thehigh costs of starting material and because of the dangers accompanying the use "of metallic sodium and benzene. the other hand, the product obtained by the second method has a boiling pointof either 156 C. or 145-146? Ci; ineither instance, this product is diiferent from a-acetylpropionitrile which. has a boiling point of 183 C. From later investigations of this second allegedm'ethod, it became clear that the product which hada boiling point of 15.6? C. was actuallya mixture of a,;3-dimetliylglycidonitrile. and a 'small quantity of aacetylpropionitrile'; the product which had a boiling point of 145 146" CL, was afi-dimethylglycidonitfile. In both cases, a acetylpropionitrile was not obtained. (Gazzetta Chimica ltaliana, Rome, 69, 378-91 1939) Chemical Abstracts, 33," 8574 (1939).) In Beilstein, 4 Auflage, 2 Ergaenzung, 3, 433, this reaction is revised and formularized as follows:

HON

Therefore, it is a principal object of this invention to provide a satisfactory method for the production of aacetylpropionitrile. 1 7

Other and further objects and advantageous features of this invention will hereinafter more fully appear from the tained by the. following reactions in aqueous or alcoholic medium:

(a) The reaction of 3-c'hlorobutanone-(2) with alkali metal cyanide. (This ketone is obtained by chlorination of methyl-ethylketone.) The amount of cyanide used is in excess of theoretical amount.

(b) The reaction of a,B-dirnethylglycidonitrile with alkali metal cyanide. (This nitrile is obtained by the reaction of 3-chlorobutanone-(2) with alkali metal cyanide.)

(c) The rearrangement of a,p-dimethylglycidonitrile by using' the catalyst such as inorganic bases, organic bases and organic acids (using solvents or no solvent).

(d) The reaction of 2-cyano-2-hydroxy-3-chlorobutane with alkali metal cyanides. (This compound is easily derived from 3-chlorobutanone-(2) or a,,8-dimethylglycidonitrile.) p

As stated in the above mentioned literature (Gazzetta Chimica Italiana, Rome, 69, 378-91 (1939)), the compound obtained by the reaction of-3-chlorobutanone-(2) with alkali metal cyanide was actually a, 8-diinethylglycidonitrile and not et-acetylpropionitrile, as originally hy- As a result of examining the above rearrangement, it was further found that other rearranging agents could'be used in addition to the alkali metal'cyanides; these other rearranging agents include inorganic bases such as hy-' droxides of alkali metals or alkaline earth metals, alkali carbonates, metal cyanides, organic bases such as pyridine, metal alcoholates, and organic acids such as acetic acid. According to further search on the mechanism of this rearrangement, it became clear, first of all, that it'was not the rearrangement of hydrogen, but that of the cyano radical, based upon the observation that the compound obtained by the similar reaction from a-ethyl-5-methyl glycidonitrile which is an analogous compou'nd to '11, 8 a-propionoylpropionitrile.

dimethylglycidonitrile was This is formularized as follows:

. 0 ON a-ethyl-B-methylglyeldonitrile a-proptonoylpropionitrile Further, as a result of tracing the rearrangement of the a Reacttonflemperature Reactmn'itme -40 minute's,- 5-15 minutes. 120

Generally speal;i-ng,-. i t seems thatthe reaction at high; temperatures yforva short time produces less-resinform matter and is better in yield.- When the reaction. is. effected in aqueous solution, benzene or other organic sole- 25 vent, whichis immiscible ,with water, maybe added, and-t if necessary, anijgemnlsifier may be added further... In such "a case,the reactiongconditions -are;sirnilar to the-3.. above, namely at a low temperature a long time is required while at a high temper-ature short reactionttim'e sufiices. Also, ,it is advisableto effectreaction at the;.. boiling poiptof the;.organi c solvent; For instance, where... benzeneis added to the; aqueous: solution, the reaction at v; 80.C. for at; minutes inmost-appropriate. In othencases; 1 where it is desired to use a solvent such-as methanohveths anol or other alcohol instead of water, the-cyanide is added preferably in powdered form and the reaction preferably proceeds' at theboih'ng pointof the solvent? For instance, in the -casesaf methanol, the, reaction should be conducted ands-3 C. .fiQl'glgp'l-S hoursei;v i 7 If the quantity of cyanide used is less than the theo retical amounnie-acetylpropionitrile3 cannot be obtained as mentioneditaboyeviglt is advisable. to use 1.5 motor more. i ,when: theitreactionis: conducted. in alcoholic me-- dium, the additiontof sbdiumealcoholate or other alkali metal; alcoholate as za:catalys't. diminishesz the quantity-of cyanide requiredaralt is preferredao usersodium cyanide" as the reactant cyanide: ail

Aftentheareaetion; been-acompleted, the reaction rnixturesmaltm e treatedaifi thednllowing wayz after cool-t 50 ll'lg fllbg mi ture-lie neutralized with hydrochloric acid," phl i .fl iiaqr othcrzmineral-Wacidtand the .medium is kept, ai-1r 3;Ci dlC.;,-.Thflf; in thelacasezofaqueousmedium; then, xture is extractedsgvithrretherpibenzene or othcr s Y organiesolventsa rlnLtheaease where watei and benzene 55 were both used, the benzene layeriis' separated.- In both- 7 cases, the organic solvent is distilled off, and thena-acetylpropionitrile is obtainedby further vacuum distillation of the residuettat78- 8O CL/2O arm; HQ. "iITjiBeEaseBr alcoholic zmedium, the reaction mixture is neutralized 50 with mineral aeidpthe; resulting solutionris filtered to' -i'e 1 move any, separatedin organiesalta and; the a1co hol: is .d tilled othrfolliowed ,byfiacuum stillationpas" deseribedsv: above t I i In the above mentioned, reaction, br-HCGiYiPIQPlODiUZll may be'obtained similarly, byreacting cyanide inaqueous or alcoholic medium, withisolat e d a,B-dimethylglycidomtrile which is easily obtained by equimolecnlar reactik in of cyanide and 3-chlorobutanone=(2)"inatjhearkdfafi nj holic medium at low temperature, preferably at lit-20 7 C. for about gner hour.-;-.;. Alternatively, the mflgtdimethylglycidonitrile may be usedas iormed witho r 1h 1' s qlat jon,-, to react with cyanide in order to obtain the desire iijnal compound. The reaction takes place in aqueous medium at atemperature of -100 C. in the short time of 5-10 75 tanQllQfQ) A minutes. When benzene is added to the aqueous medium,

or when alcoholic medium alone is used, the reaction is V carriedout gently at the boiling point of the medium for Vz-1 hour.

'In the case of alcoholic medium, the addition of alkalimetal alcoholate diminishesthe quantity of cyanides required just as in the manner mentioned above.

When isolated a,fl-dirnethylglycidonittile is used as a reactant, besides the above mentioned conditions of reaction, inorganic bases such as hydroxides of alkali metals or alkaline earth metals, alkalicarbonates, metal cyanides, organic bases such as pyridine, metal alcoholates, or organic acids such as acetic acid may be used; the re-, action mixture is heated, possibly in the presence of water or organic solvent, andsthe starting material is converted into a-acetylpropionitrile.,, The, reaction ,temperature should be, in case of using solvent, theboiling point of that solvent, and in case of no solvent, higher than that, preferablyat 1.00? to C. f

Further,,-;from 2 cyano; Z-hydroxy- 3w chlo robuta ne; which-is, easily obtained by adding-hydrogen, cyanide :to 1'. 3-chlorobutanone-(2), or by adding hydrogen chloride, to a,fi diniethylglycidonitrile, a-acetylpropionitrile maybe obtainedby means of cyanides, as in the" case of ,3: chlorobutanone-(2). This reaction is formularizeda as,

follows CNS LH Q. T 7 FCHL 0 a i 2-c 0-2-1 drnx ril ilorobgtane 0H,... H H a rearrange- ,7 '0' l O N. a fi-dtmethylglyctdm a-acetylpropiontnitrile i trile (Inferred intermediate)- w The following examples are given simply to illustrate our invention but not in any way to limitjits scoper Partsi mentioned therein represents ,ratio of aveightg,

Example '1 To-theaqueoussolution of 22 parts of sodium cyanide and 40 parts of water, 20 parts of 3-chlorobntanone-(Z) v arej added dropwi se, under cooling with ice, and reaction, is conducted at IO-20 C. for one hour. Afterwardgthe temperature is raised and reaction is continued for",

10 minutesjat 9011001 C. Then, after addingflo of f at i th react n ia te s .mu ta lzediv flt. rhu ac dm s ool nstr m i ez iter ardsaiii 'i ir s extrac ed hiether, and f en rlqfil P t of e v opi n t l iwhithf -tl tills at 78-80? C./20"mm. Hg are obtained by vacuum distillation', The yield is 41.1% basedon S-chlorobu;

Example 2 the benzene laye g is separatedand benzege is distilled ofi. "Thnthegresidue is treatedeasinEXample 1, and 7 parts of e-acetylpropionitriler;areeobtained. The yield is l8- ?as 9 it st b essaszQl-lwmpled To the aqueous solution of 122 .5 parts of sodium t eid ss tdfri tsst \ra r.; .06 -4-m qtfiahler hua.

assa'oa tanone-(2) are added dropwise under cooling with ice. Afterwards, the mixture is heated to 90-100 C. where it is kept for 15 minutes. Then 250 parts of cold water are added, and the mixture is-neutralized with sulphuric acid, under cooling from outside. Afterwards, the product is treated asin Example 1 and 31 parts of a-acetylpropionitrileare obtained. r The yield is 32% based on 3-chlorobutanone-(2).

Example 4 To the aqueous solution of 10 parts of sodium cyanide and 20 parts of water, 20 parts of 3-chlorobutanone-(2)" are added dropwise, under cooling with ice. Afterwards, the reaction is performed at 10-20 CV-for one hour. Then, the aqueous solution of 12 parts of sodium cyanide and 24 parts of water is added, and the temperature is raised to 90100 C. where the reaction is continued for 10 minutes. Thereafter, 40 parts of water are added, and the mixture is neutralized with sulphuric acid, under cooling from-outside. Afterwards, the product is treated as in Example 1 and 7.3 parts of a-acetylpropionitrile are obtained. The yield is 40% based on 3-chlor obutanone-(2).

Example 5 To 80 parts of methanol, 21 parts of powdered sodium cyanide are added, and 20 parts of 3-chlorobutanone-(2) are brought into the mixture by stirring, while maintaining the mixture at 65 C., and the reaction is conducted for one hour. Afterwards, the reaction mixture is neutralized with sulphuric acid under cooling. After filtration, methanol is distilled oif from the filtrate. Then, the residue is treated in the similar way as mentioned above and 8.9 parts of a-acetylpropionitrile are obtained. The yield is 48.8% based on 3-chlorobutanone-(2).

Example 6 To 80 parts of methanol, 13.8 parts of powdered sodium cyanide and 20 parts of 3-chlorobutanone-(2) are added, and 11.1 parts of sodium alcoholate are brought dropwise into the mixture by stirring, and the reaction is continued for one hour at 65 C. Thereafter, the product is treated as in Example 5, and 8.8 parts of a-acetylpropionitrile are obtained. The yield is 48.3% based on 3-chlorobu-tanone-(2).

Example 7 To the aqueous solution of 59 parts of sodium cyanide and 118 parts of water, 100 parts of benzene, 2 parts of Turkey red oil and 97 parts of a,fl-dimethylglycidonitrile are added, and the mixture is allowed to react at 80 C., for 30 minutes. Then, 100 parts of water are added, and the mixture is neutralized with'sulphuric acid, under cooling. After the benzene layer is separated and benzene is distilled off, 44.6 parts of u-acetylpropionitrile are obtained by the similar treatment as mentioned above. The yield is 46% based on a,p-dimethylglycidonitrile.

Example 9 To 80 parts of absolute ethanol, 11 parts of powdered sodium cyanide are added; the mixture is stirred and maintained at 80 C.; then, 20 parts of a,;9-dimethylglyci donitrile are added dropwise. After the reaction is con- After the reaction is Y tinned for one hour, the reaction mixture is treated as in Example 5, and 9.6 parts of -acetylpropionitrile are obtained. The

yield is 48% based on a,p-dimethylglycidonitrile.

Example 10 The aqueous solution of 11 parts of sodium carbonate and 25. parts of water is heated to about C., 20 parts of a,p-dimethylglycidonitrile are added to it, and the mixture is allowed to react at -100 C. for 30 minutes. Afterwards, the mixture is neutralized with sulphuric acid, under cooling, and extracted with ether; the ether layer is separated and ether is distilled 01f. Thereafter, the distillation residue is treated as in the previous example and 6 parts of a-acetylpropionitrile are obtained. In this case, 5 parts of raw material are recovered. The yield is 40% based on a,fl-dimethylglycidonitrile (taking into consideration the recovery of raw material).

Example 11 To 25 parts of 1:,19-dimethylglycidonitrile, 10 parts of calcium hydroxide are added and the mixture is allowed to react at 140150 C. for five hours. Then 6.8 parts of a-acetylpropionitrile are obtained by vacuum distillation. In this case,'2.6 parts of raw material are recovered. The yield is 30.3% based on a,/i-dimethylglycidonitrile (taking into consideration the recovery of raw materials).

Example 12 propionitrile are obtained *by the vacuum distillation. The V yield is 15.6% based on cap-dimethylglycidonitrile.

Example 13 T0133 parts of Z-cyano-Z-hydroxy-3-chlorobutane, 400 parts of ethanol are added. To this mixture, an aqueous solution consisting of 108 parts of sodium cyanide and 300 parts of water is added, and the mixture is allowed to react at room temperature for three hours and then at 80 C. for 30 minutes. After ethanol is distilled off, the reaction mixture is neutralized with sulphuric acid, under cooling and extracted with ether. After ether is distilled off, the residue is treated in the similar way as mentioned above, and 34 parts ofa-acetylpropionitrile are obtained. The yield is 35% based on 2-cyano-2-hydroxy-3-chlor0butane.

Whereas the present invention has been described with particular reference to the examples included herein, other modifications apart from those described or suggested herein may be made within the spirit of this invention.

We claim:

1. The process for preparing a-acetylpropionitrile, which comprises reacting 3-chlorobutanone-(2) with an aqueous solution containing more than an equimolar which comprises reacting at a temperature between 35 and 1 C. 3-chlorobutanone-(2) with an aqueous solution containing at least about 1.5 moles of an alkali metal cyanide per mole of chlorobutanone.

3. The process of claim 2, wherein a water-immiscible solvent is also present, the a-acetylpropionitrile entering the water-immiscible solvent phase.

4. The process for preparing a-acetylpropionitrile, which comprises reacting at a temperature between 35 and 100 C. 3-chlorobutanone-(2) with at least about 1.5 times the molar amount of an alkali metal cyanide in the presence of an alcohol as solvent.

5. The process of claim 4, wherein the alcohol solvent is methanol.

6. The process of claim 4, wherein an alkali metal alcoholate is also present in the course of the reaction.

7. The process for preparing a-acetylpropionitrile, which comprises contacting 3-chlorobutanone-(2) with a being'first added and the balance of the cyanide being sub:

sequently added.

8. The process for preparing a-acetylpropionitrile, whichcomprises heating at a temperature of 35 to 100 C.

3-chlorobutanone-(2) with approximately an equimolar amount of an alkali metal cyanide in the presence of a solvent selected from the group consisting of an alcohol t and water, thereby forming u,fl-dimethylglycidonitrile, and

then directly adding to the reactionmass a catalyst selected from the group consisting of inorganic basic compounds,

. 8 1 organic basic compounds, and organic acidic compounds, whereby the dimethylglycidonitrile is rearranged to a-acetylpropionitrile.

9. The processof claim 8, wherein the rearrangement catalyst is an alkali inetal cyanide. x 10. The process of claim 8, wherein the rearrangement catalyst is'an alkaline earth metal hydroxide,

llz/[he process of-clairrr 8, wherein the solvent is an alcohol and the rearrangement catalyst is a mixture of an 10 alkali metal cyanide and an alkali metal alcoholate.

No references cited. 

1. THE PROCESS FOR PREPARING A-ACETYLPROPIONITRILE, WHICH COMPRISES REACTING 3-CHLOROBUTANONE-(2) WITH AN AQUEOUS SOLUTION CONTAINING MORE THAN AN EQUIMOLAR AMOUNT OF AN ALKALI METAL CYANIDE AT A TEMPERATURE BETWEEN 35 AND 100*C. 